Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity

Obesity results from an imbalance between energy intake and expenditure. This study identifies a pathway linking peripheral Y1 receptors (Y1R) to energy expenditure control. Selective peripheral Y1R antagonism using BIBO3304 significantly reduces body weight gain by enhancing energy expenditure and reducing fat mass, increasing brown adipose tissue (BAT) thermogenesis (elevated UCP1) and promoting white adipose tissue browning in mice and humans. Adipocyte-specific Y1R ablation also protects against diet-induced obesity and improves glucose homeostasis via changes in BAT Akt activity. These findings suggest peripheral Y1R antagonism as a potential obesity treatment.

Chenxu Yan, Tianshu Zeng, Kailun Lee, Max Nobis, Kim Loh, Luoning Gou, Zefeng Xia, Zhongmin Gao, Mohammed Bensellam, Will Hughes, Jackie Lau, Lei Zhang, Chi Kin Ip, Ronaldo Enriquez, Hanyu Gao, Qiao-Ping Wang, Qi Wu, Jody J. Haigh, D. Ross Laybutt, Paul Timpson, Herbert Herzog, Yan-Chuan Shi